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Sheng Li Xue Bao : [Acta Physiologica... Jun 2024The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging...
The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining. Western blot was used to detect the protein expression levels of agglutinate protein (Agrin), low-density lipoprotein receptor-related protein 4 (Lrp4), muscle- specific kinase protein (MuSK), downstream tyrosine kinase 7 (Dok7), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target rapamycin (p-mTOR), and phosphorylated forkhead box O1 (p-FoxO1) in rat gastrocnemius muscles. The results showed that, endurance and resistance exercises increased the wet weight ratio of gastrocnemius muscle in the aging rats. The protein expression of S100B in the R group was significantly higher than those in the O and EN groups. Proteins related to NMJ function, including Agrin, Lrp4, MuSK, and Dok7 were significantly decreased in the O group compared with those in the Y group. Resistance exercise up-regulated these four proteins in the aging rats, whereas endurance exercise could not reverse the protein expression levels of Lrp4, MuSK and Dok7. Regarding skeletal muscle-related proteins, the O group showed down-regulated p-Akt, and p-mTOR protein expression levels and up-regulated p-FoxO1 protein expression level, compared to the Y group. Resistance and endurance exercises reversed the changes in p-mTOR and p-FoxO1 protein expression in the aging rats. These findings demonstrate that both exercise modes can enhance NMJ function, increase protein synthesis and reduce the catabolism of skeletal muscle-related proteins in aging rats, with resistance exercise showing a more pronounced effect.
Topics: Animals; Male; Aging; Rats; Rats, Sprague-Dawley; Muscle, Skeletal; Physical Conditioning, Animal; Neuromuscular Junction; Muscle Proteins; Resistance Training; Forkhead Box Protein O1
PubMed: 38939932
DOI: No ID Found -
Annals of Ibadan Postgraduate Medicine Apr 2024A major modifiable risk factor for atherosclerotic cardiovascular disease is abnormalities in lipid and lipoprotein metabolism which are frequently seen in HIV as well...
BACKGROUND AND OBJECTIVE
A major modifiable risk factor for atherosclerotic cardiovascular disease is abnormalities in lipid and lipoprotein metabolism which are frequently seen in HIV as well as its treatment. Apo-E is a protein that is important in plasma lipid homeostasis and its genetic alleles have been shown to contribute to lipid abnormalities. We examined for the effect of Apo-E gene polymorphisms on plasma lipid levels in PLHIV on protease inhibitor therapy.
METHODS
This was a cross-sectional study conducted among adult persons living with HIV. Lipid profile, Apo-B and Apo-A were measured in fasting plasma. Amplification and analysis of Apo-E genotypes were determined using the Seeplex Apo-E ACE genotyping kit. Differences in quantitative values were compared with non-parametric analysis methods.
RESULTS
Eighty-four persons were recruited into the study, 75% of whom were virally suppressed. The 3 homozygous genotypes had significantly different levels of low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo-B) and Apolipoprotein A1 (Apo-A1). Persons with apo ε2/ε2 had higher LDL-C compared to those with apo ε3/ε3 (3.26 (3.61) mmol/L vs. 2.76 (1.28) mmol/L, p = 0.010). Those with apo ε4/ε4 had lower Apo-A1 compared to those with apo ε3/ε3 (0.84 (0.48) g/dL vs. 1.27 (0.70) g/dL, p =0.009). Compared with the same group, the heterozygous genotype, apo ε2/ε3 had lower triglyceride levels :1.33 (0.65) mmol/ L vs. 1.86 (1.11) mmol/L, p = 0.045.
CONCLUSION
Polymorphisms in the Apo-E gene may have significant influences on plasma lipid and apolipoprotein levels in PLHIV on PI therapy. This may have implications for the assessment of risk for cardiovascular disease.
PubMed: 38939889
DOI: No ID Found -
JACC. Advances Jan 2024Low-density lipoprotein cholesterol (LDL-C) is used to guide lipid-lowering therapy after a myocardial infarction (MI). Lack of LDL-C testing represents a missed...
BACKGROUND
Low-density lipoprotein cholesterol (LDL-C) is used to guide lipid-lowering therapy after a myocardial infarction (MI). Lack of LDL-C testing represents a missed opportunity for optimizing therapy and reducing cardiovascular risk.
OBJECTIVES
The purpose of this study was to estimate the proportion of Medicare beneficiaries who had their LDL-C measured within 90 days following MI hospital discharge.
METHODS
We conducted a retrospective cohort study of Medicare beneficiaries ≥66 years of age with an MI hospitalization between 2016 and 2020. The primary analysis used data from all beneficiaries with fee-for-service coverage and pharmacy benefits (532,767 MI hospitalizations). In secondary analyses, we used data from a 5% random sample of beneficiaries with fee-for-service coverage without pharmacy benefits (10,394 MI hospitalizations), and from beneficiaries with Medicare Advantage (176,268 MI hospitalizations). The proportion of beneficiaries who had their LDL-C measured following MI hospital discharge was estimated accounting for the competing risk of death.
RESULTS
In the primary analysis (mean age 76.9 years, 84.4% non-Hispanic White), 29.9% of beneficiaries had their LDL-C measured within 90 days following MI hospital discharge. Among Hispanic, Asian, non-Hispanic White, and non-Hispanic Black beneficiaries, the 90-day postdischarge LDL-C testing was 33.8%, 32.5%, 30.0%, and 26.0%, respectively. Postdischarge LDL-C testing within 90 days was highest in the Middle Atlantic (36.4%) and lowest in the West North Central (23.4%) U.S. regions. In secondary analyses, the 90-day postdischarge LDL-C testing was 26.9% among beneficiaries with fee-for-service coverage without pharmacy benefits, and 28.6% among beneficiaries with Medicare Advantage coverage.
CONCLUSIONS
LDL-C testing following MI hospital discharge among Medicare beneficiaries was low.
PubMed: 38939806
DOI: 10.1016/j.jacadv.2023.100753 -
American Journal of Preventive... Jun 2024The American Heart Association's (AHA) Life's Essential 8 (LE8) score is a helpful tool to quantify cardiovascular health (CVH) metrics. We sought to assess sex...
BACKGROUND
The American Heart Association's (AHA) Life's Essential 8 (LE8) score is a helpful tool to quantify cardiovascular health (CVH) metrics. We sought to assess sex differences in relation to LE8 and its components along with association with mortality.
METHODS
The National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018 was utilized to evaluate the prevalence of health metrics included in LE8 among adult participants > age 18, stratified by sex. We categorized overall CVH, health factors, and health behaviors into 3 levels (low: <50, moderate: 50 -79, high: ≥80) following the AHA's algorithm. Health metrics were further subdivided into health behaviors (diet, physical activity, nicotine exposure, and sleep) and health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure). LE8 scores were also evaluated based on age, race/ethnicity, and socioeconomic status. Cox proportional hazard models were used to evaluate the association between the levels of CVH and risk of all-cause and cardiovascular mortality, with adjustment for age group and race.
RESULTS
Among 22,761 participants, 52 % were female. Overall CVH score was similar in both females and males (65.8 vs. 65.9). Females had higher health factors score (64.3 vs. 63.1, < 0.001) and lower health behaviors score (67.2 vs 68.6, < 0.001). Amongst individual metrics, blood pressure score was higher in females (73.2 vs. 67.7, < 0.001) while males had higher physical activity score (70.6 vs. 54.9, < 0.001). For individuals under 65 years of age, overall CVH and health factors scores were higher in females while in those age 65 or older, males had higher scores. The most prominent sex differences were noted in non-Hispanic Black females who had significantly lower CVH scores than Black males (62.6 vs. 74.7, respectively, < 0.001. High LE8 scores vs. low LE8 scores demonstrated lower all-cause (HR 0.37 vs 0.35) and CV mortality (HR 0.35 vs. 0.36) in both males and females, respectively (p-interaction 0.21 and 0.28). High health behaviors scores also demonstrated a significant association with lower all-cause (0.34 vs. 0.24) and CV mortality (HR 0.47 vs. 0.26) in both males and females, respectively (p-interaction 0.20 and 0.11).
CONCLUSIONS
We demonstrate important sex differences in CVH metrics along with notable variations based on age and race/ethnicity. Furthermore, we highlight that CVH metrics including health factors and health behaviors are associated with mortality in both females and males. These findings underscore the importance of designing and implementing effective strategies for both sexes, aimed at targeting these specific factors.
PubMed: 38939696
DOI: 10.1016/j.ajpc.2024.100685 -
JACC. Advances Sep 2023
PubMed: 38939484
DOI: 10.1016/j.jacadv.2023.100559 -
JACC. Advances Aug 2023Cardiac rehabilitation (CR) modeled care is recommended for patients with breast cancer to mitigate risk of cardiotoxicity. However, the cardiovascular impact of...
BACKGROUND
Cardiac rehabilitation (CR) modeled care is recommended for patients with breast cancer to mitigate risk of cardiotoxicity. However, the cardiovascular impact of CR-modeled interventions has not been studied.
OBJECTIVES
The purpose of this study was to evaluate if a multidisciplinary model of CR reduces cardiotoxicity and improves cardiovascular risk in patients undergoing breast cancer treatment.
METHODS
We randomly assigned patients with stage I to III breast cancer scheduled to receive anthracycline and/or trastuzumab-based chemotherapy to the CR intervention (n = 37) or usual care (n = 37). The intervention included guideline-directed management of cardiovascular risk factors, dietary counselling, and supervised exercise for 52 weeks. Cardiac magnetic resonance imaging, cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, and serum biomarkers were acquired at baseline and 52 weeks.
RESULTS
There was no difference in the primary outcome, left ventricular ejection fraction (LVEF), between groups at 52 weeks (61% ± 6%). Other markers of cardiotoxicity, including high-sensitivity troponin I and brain natriuretic peptide, were similar between groups. However, total cholesterol (5.2 ± 0.8 mmol/L to 4.7 ± 0.8 mmol/L, = 0.002) and low-density lipoprotein (3.0 ± 0.7 mmol/L to 2.4 ± 0.7 mmol/L, < 0.001) decreased in the intervention group at 52 weeks and were unchanged in usual care. In all patients, adverse cardiac and metabolic changes occurred over 52 weeks including reductions in LVEF, left ventricular mass, high-density lipoprotein, lean body mass, insulin-like growth factor-1, as well as increased triglycerides, whole-body and truncal fat mass (all < 0.050).
CONCLUSIONS
The CR-modeled intervention had no effect on LVEF or biomarkers of cardiotoxicity. Future lifestyle intervention trials in patients with breast cancer should consider targeting other risk factors associated with incident cardiovascular disease. (Multidisciplinary Team IntervenTion in CArdio-ONcology [TITAN Study] [TITAN]; NCT01621659).
PubMed: 38939428
DOI: 10.1016/j.jacadv.2023.100424 -
Frontiers in Microbiology 2024This study aimed to explore whether G423 could improve growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites. A total...
This study aimed to explore whether G423 could improve growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites. A total of 640 1-day-old AA broilers were randomly divided into 4 groups [Control (CON), Lac_L, Lac_H, and ABX]. Average daily gain (ADG), average daily feed intake (ADFI), feed conversion ratio (FCR), breast muscle, thigh muscle, and abdominal fat pad were removed and weighed at 42 days of age. Serum was obtained by centrifuging blood sample from jugular vein (10 mL) for determining high-density lipoprotein (HDL), total cholesterol (TC), low-density lipoprotein (LDL), and triglyceride (TG) using ELISA. The ileal contents were harvested and immediately frozen in liquid nitrogen for 16S rRNA and LC-MS analyses. Then, the results of 16S rRNA analysis were confirmed by quantitative polymerase chain reaction (qPCR). Compared with the CON group, FCR significantly decreased in the Lac_H group ( < 0.05) in 1-21 days; ADG significantly increased and FCR significantly decreased in the Lac_H group ( < 0.05) in 22-42 days. 42 days weight body and ADG significantly increased in the Lac_H group ( < 0.05) in 42 days. Abdominal fat percentage was significantly decreased by G423 ( < 0.05), the high dose of G423 significantly decreased the serum of TG, TC, and LDL level ( < 0.05), and the low dose of G423 significantly decreased the serum of TG and TC level ( < 0.05). A significant difference in microbial diversity was found among the four groups. Compared with the CON group, the abundance rates of in the Lac_H group were significantly increased ( 0.05). The global and overview maps and membrane transport in the Lac_L, Lac_H, and ABX groups significantly changed versus those in the CON group ( < 0.05). The results of LC-MS demonstrated that could significantly improve the levels of some metabolites (6-hydroxy-5-methoxyindole glucuronide, 9,10-DiHOME, -Acetyl-l-phenylalanine, and kynurenine), and these metabolites were involved in four metabolic pathways. Among them, the pathways of linoleic acid metabolism, phenylalanine metabolism, and pentose and glucuronate interconversions significantly changed ( < 0.05). G423 could ameliorate growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites.
PubMed: 38939183
DOI: 10.3389/fmicb.2024.1381756 -
JACC. Advances Nov 2023Guideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor...
BACKGROUND
Guideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i) monoclonal antibodies can help further reduce LDL-C and major adverse cardiovascular events (MACE) although differences in efficacy by sex and type are less understood.
OBJECTIVES
The authors sought to determine if there are differences in the efficacy of LDL-C lowering and reduction in the risk of MACE by sex and type of PCSK9i.
METHODS
A comprehensive literature search was done through October 17, 2022, for published trials comparing PCSK9i vs control. Outcomes assessed were LDL-C reduction and incidence of MACE following the use of PCSK9i vs placebo, stratified by sex and type of PCSK9i used.
RESULTS
We identified 16 trials with 54,996 adults, and 15,143 (27.5%) of them were female. PCSK9i significantly reduced MACE compared to placebo in both women (HR: 0.86, 95% CI: 0.74-0.97, < 0.001) and men (HR: 0.85, 95% CI: 0.79-0.91, < 0.001) with no significant sex difference (MD -0.01, 95% CI: -0.14 to -0.13, = 0.930). PCSK9i also significantly reduced LDL-C levels in both sexes at 12 weeks (females: MD -62.57, 95% CI: -70.24 to -54.91, < 0.001; males: MD -66.19, 95% CI: -72.03 to -60.34, < 0.001) and 24 weeks (females: MD -47.52, 95% CI: -52.94 to -42.09, < 0.001; males: MD -54.07, 95% CI: -59.46 to -48.68, < 0.001). Significant sex difference was seen in the LDL reduction of PCSK9i for both 12 weeks (males vs females: MD -4.55, 95% CI: -7.34 to -1.75, < 0.01) and 24 weeks (males vs females: MD -7.11, 95% CI: -9.99 to -4.23, < 0.001).
CONCLUSIONS
The use of PCSK9i results in significant LDL-C and MACE reduction in both males and females. While there is no significant sex difference in MACE reduction, LDL-C reduction is greater in males than in females. Our data support the equal use of PCSK9i in all eligible patients, regardless of sex.
PubMed: 38938736
DOI: 10.1016/j.jacadv.2023.100669 -
JACC. Advances Nov 2023Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder characterized by increased circulating low-density lipoprotein cholesterol and accelerated...
BACKGROUND
Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder characterized by increased circulating low-density lipoprotein cholesterol and accelerated atherosclerosis. Even among this high-risk group, prior studies note considerable variability in risk of coronary artery disease (CAD).
OBJECTIVES
The purpose of this study was to evaluate the cumulative impact of many common DNA variants-as quantified by a polygenic score-on incident CAD among individuals carrying a HeFH variant.
METHODS
We analyzed data from a prospective cohort study of 1,315 individuals who carried a HeFH variant and 1,315 matched family noncarriers derived from a nationwide screening program in the Netherlands, with subsequent replication in 151,009 participants of the UK Biobank.
RESULTS
Despite identification and lipid management within the Dutch screening program, 84 (6.4%) of HeFH variant carriers developed CAD as compared to 45 (3.4%) of matched family members (median follow-up 10.2 years, HR 1.88, 95% CI: 1.31-2.70). Among HeFH variant carriers, a polygenic score was associated with CAD with an effect size similar to low-density lipoprotein cholesterol - HR of 1.35 (95% CI: 1.07-1.70) and 1.41 (95% CI: 1.17-1.70) per standard deviation increase, respectively. When compared to noncarriers, CAD risk increased from 1.24-fold (95% CI: 0.64-2.34) to 3.37-fold (95% CI: 2.11-5.36) across quintiles of the polygenic score. A similar risk gradient, 1.36-fold (95% CI: 0.65-2.85) to 2.88-fold (95% CI: 1.59-5.20), was observed in 429 carriers in the UK Biobank.
CONCLUSIONS
In 2 cohort studies involving 1,744 individuals with genetically confirmed HeFH - the largest study to date - risk of CAD varied according to polygenic background, in some cases approaching the risk observed in noncarriers.
PubMed: 38938725
DOI: 10.1016/j.jacadv.2023.100662 -
JACC. Advances Nov 2023Homozygous familial hypercholesterolemia (HoFH) is characterized by early-onset atherosclerotic cardiovascular disease due to the high low-density lipoprotein...
BACKGROUND
Homozygous familial hypercholesterolemia (HoFH) is characterized by early-onset atherosclerotic cardiovascular disease due to the high low-density lipoprotein cholesterol (LDL-C) burden. Patients with null-null low-density lipoprotein receptor () variants respond poorly, if at all, to statins and proprotein convertase subtilisin/kexin type 9 inhibitors, which act by upregulating expression. The 24-week double-blind treatment period (DBTP) of the phase 3 ELIPSE HoFH (Evinacumab Lipid Studies in Patients with Homozygous Familial hypercholesterolemia; NCT03399786) study demonstrated significant LDL-C reductions in patients with HoFH; LDL-C reductions were also observed in those with null-null mutations.
OBJECTIVES
The purpose of this study was to evaluate longer-term efficacy and safety of evinacumab in patients with HoFH from the ELIPSE HoFH study.
METHODS
Patients with HoFH on stable lipid-lowering therapies (LLTs) ± lipoprotein apheresis and screening LDL-C ≥70 mg/dL who completed the DBTP entered the 24-week open-label treatment period (OLTP) and received intravenous evinacumab 15 mg/kg every 4 weeks. OLTP results were summarized descriptively.
RESULTS
A total of 64 patients completed the DBTP and received open-label evinacumab. Despite multiple LLTs, the mean baseline LDL-C at DBTP entry was 250.5 ± 162.3 mg/dL. From baseline to week 48 (end of OLTP), evinacumab reduced mean LDL-C by 46.3% (mean reduction, 134.3 ± 117.3 mg/dL), with similar mean LDL-C reductions for patients with null-null (47.2%) and non-null variants (45.9%). Adverse events occurred in 47 (73.4%) patients; 4 (6.3%) patients experienced adverse events considered evinacumab-related (drug hypersensitivity, infusion-related reaction and asthenia, generalized pruritis, and muscle spasms).
CONCLUSIONS
In patients with HoFH, evinacumab demonstrated substantial and sustained LDL-C reduction regardless of LDLR function, and was generally well tolerated.
PubMed: 38938723
DOI: 10.1016/j.jacadv.2023.100648